16-1240985-C-T

Position:

chr16-1240985-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_003294.4(TPSAB1):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000059 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TPSAB1
NM_003294.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.575

Variant links:

Genes affected

TPSAB1 (HGNC:12019): (tryptase alpha/beta 1) Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. These genes are characterized by several distinct features. They have a highly conserved 3' UTR and contain tandem repeat sequences at the 5' flank and 3' UTR which are thought to play a role in regulation of the mRNA stability. These genes have an intron immediately upstream of the initiator Met codon, which separates the site of transcription initiation from protein coding sequence. This feature is characteristic of tryptases but is unusual in other genes. The alleles of this gene exhibit an unusual amount of sequence variation, such that the alleles were once thought to represent two separate genes, alpha and beta 1. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha tryptases predominate. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. [provided by RefSeq, Jul 2008]

TPSAB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058300525).

BP6

Variant 16-1240985-C-T is Benign according to our data. Variant chr16-1240985-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3328344.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPSAB1	NM_003294.4 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	2/6	ENST00000338844.8	NP_003285.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPSAB1	ENST00000338844.8 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	2/6	1	NM_003294.4	ENSP00000343577	P2	Q15661-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150776

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000331

AC:

AN:

60378

Hom.:

AF XY:

0.0000330

AC XY:

AN XY:

30342

show subpopulations

Gnomad AFR exome

AF:

0.000352

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000587

AC:

AN:

1363166

Hom.:

Cov.:

AF XY:

0.00000741

AC XY:

AN XY:

674342

show subpopulations

Gnomad4 AFR exome

AF:

0.000259

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000464

AC:

AN:

150776

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73522

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.42

DANN

Benign

0.20

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.39

T;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.69

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.91

N;N

REVEL

Benign

0.086

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

B;.

Vest4

0.068

MVP

0.088

MPC

0.061

ClinPred

0.035

GERP RS

-2.9

Varity_R

0.025

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over